SARS-CoV-2 infection of hACE2 transgenic mice causes severe lung inflammation and impaired function

By Emma S. Winkler, Adam Leitman Bailey, Natasha M. Kafai, S. Nair, B. McCune, Jinsheng Yu, J. Fox, Rita E. Chen, J. T. Earnest, Shamus P. Keeler and 7 more. Nature Immunology, 2020

694 citations recorded by the source corpus.

Although animal models have been evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, none have fully recapitulated the lung disease phenotypes seen in humans who have been hospitalized. Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of nuclear factor-κB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures. Diamond and colleagues generate a K18-hACE2 model of SARS-CoV-2 infection that shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/939c1703475931712a34467ef085ac0f778da845

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. R. Malireddi
2. T. Kanneganti
3. Michael S. Diamond
4. Wenshuai Wang
5. Anna Marie Pyle

In Infectious Diseases

1. T. Kanneganti
2. Wenshuai Wang
3. Anna Marie Pyle

Citations in the corpus

• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, positive): “We first tested the prophylactic efficacy of COV2-2676 or COV2-2489 in a well-defined model of SARS-CoV-2 infection in hACE2-expressing transgenic mice (Winkler et al., 2020).”
• Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes (2020, positive): “160 Cell 184, 149–168, January 7, 2021 of this treatment during SARS-CoV-2 infection, we used amurine SARS-CoV-2 infection model (Winkler et al., 2020).”